Deep Brain Stimulation

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FIGURE 4 Microelectrode recording of the extracellular action potentials of a globus pallidus internal segment neuron in response to deep brain stimulation in the vicinity of the subthalamic nucleus. This is a 30-second baseline recording followed by 30 seconds of stimulation and then recording for an additional 30 seconds.

Kumar et al. (19) reported 22 PD patients who were treated with either unilateral (n 5) or bilateral (n 17) GPi stimulation. Evaluations performed in the medication off stimulation on state at six months reported a 32 improvement in UPDRS motor scores and a 40 improvement in UPDRS activities of daily living (ADL) scores compared to baseline medication off scores. There was also a 68 reduction in dyskinesia. The Deep Brain Stimulation for Parkinson's Disease Study Group (16) reported a multinational, prospective study of bilateral GPi stimulation in PD. Forty-one patients were enrolled and electrodes were implanted in 38 patients. Two patients had cerebral hemorrhages and one patient had intraoperative confusion. In comparison to baseline, there was a significant improvement of 33 in UPDRS motor scores in the medication off stimulation on state. More specifically, tremor was reduced by 59 , rigidity was reduced 31 , bradykinesia was reduced 26 , gait improved by 35 , and postural...

Multiple reports have demonstrated the short-term benefits of STN DBS in controlling the cardinal features of PD and reducing dyskinesia and antiparkinsonian medications (16,24-31). One of the largest studies was conducted by the Deep Brain Stimulation for Parkinson's Disease Study Group (16). This was a multicenter study in which 96 PD patients received bilateral STN DBS and 91 completed the Several studies have demonstrated the long-term benefits of STN DBS (23,32-37) (Table 2). Rodriguez-Oroz et al. (23) examined 49 PD patients who received bilateral STN DBS as part of the original Deep Brain Stimulation for Parkinson's Disease Study Group trial (16), three to four years after initial implant. They demonstrated a 43 improvement in UPDRS ADL scores and a 50 improvement in UPDRS motor scores in the medication off stimulation on condition compared to the baseline medication off state. More specifically, there was an 87 improvement in tremor, a 59 improvement in rigidity, a 42...

Many studies of deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus internus (GPi), and ventral intermediate (Vim) nucleus of the thalamus have reported dysarthria and dysphagia as side effects (88-90). Several studies examined specific aspects of voice, speech, swallowing and related orofacial, and respira-tory-laryngeal functions associated with DBS treatment of PD. Santens et al. (91) found that left-brain stimulation had a profound negative effect on prosody, articulation, and intelligibility not seen with right-brain stimulation. With bilateral stimulation, no differences in speech characteristics were observed on- and off-stimulation. Wang et al. (92) also studied the effects of unilateral STN DBS on respiratory phonatory subsystems of speech production in PD. Speech recordings were made in the medication-off state at baseline and three months post-DBS with stimulation-on and -off, in six right-handed patients. Three patients who received left-brain...

The treatment of choice for RBD is clonazepam, a benzodiazepine, although the mechanism is unknown and there are no controlled trials (13). Other drugs thought to be helpful for RBD include pramipexole, levodopa, carbamazepine, donepezil, and melatonin (64,89-91). Caution needs to be exercised with the use of clonazepam, as in some cases, RBD may be confused with sleep apnea, which can be worsened by clonazepam. Nighttime dosing with drugs such as selegiline may aggravate RBD. Others have reported a paradoxical worsening of RBD with deep brain stimulation (DBS) of the subthalamic nucleus (STN) (92).

Nucleus (STN) deep brain stimulation (DBS) surgery only when the stimulators were turned on (43), leading the authors to hypothesize that this resulted from stimulation of limbic fibers near the STN. Finally, a functional MRI study demonstrated greater activation in the frontal lobe in PD patients with chronic visual hallucinations compared to nonhallucinators (44). The exact contribution of these neurotransmitters and structures to the genesis of psychosis is unclear.

Three-dimensional autonomic space representation of chronotropic control of the heart. The effector surface depicts the heart period level for all possible loci within the autonomic plane. Parasympathetic and sympathetic axes are scaled in proportion to the extent of their functional range of control, and the curvature in the surface reflects nonlinear-ities in these controls. Beta (on the abscissa) illustrates the heart period in the absence of autonomic control. The curved lines on the autonomic plane are isofunctional contour lines, which represent varying combinations of sympathetic and parasympathetic control that yield comparable heart period effects. Reprinted from Behavioral Brain Research, 94, Berntson, Sarter, and Cacioppo Anxiety and Cardiovascular Reactivity The Basal Forebrain Cholinergic Link, 225-248. Copyright (1998), Elsevier. FIGURE 12.2. Three-dimensional autonomic space representation of chronotropic control of the heart. The effector surface depicts...

The administration of MPTP through a number of different dosing regimens has led to the development of several distinct models of parkinsonism in the nonhuman primate. Each model is characterized by unique behavioral and neurochem-ical parameters. As a result, numerous studies addressing a variety of hypotheses have been conducted. These studies consist of new pharmacological treatments, transplantation, mechanisms of motor complications, deep brain stimulation, behavioral recovery, cognitive impairment, and the development of novel neuro-protective and restorative therapies. For example, in some models, there is profound striatal dopamine depletion and denervation with little or no dopaminergic axons or terminals remaining. This model provides an optimal setting to test fetal tissue grafting since the presence of any tyrosine hydroxylase positive axons or sprouting cells would be due to transplanted tissue survival. Other models have less extensive dopamine depletion and only partial...

Many of the costs associated with the creation of an ablative lesion and placement of a deep brain stimulator are similar (Table 2). These include preoperative imaging, operating room time for burr hole creation and target identification and hospital stay. The time difference between that needed for Table 2 Costs of Ablation Versus Deep Brain Stimulation Table 2 Costs of Ablation Versus Deep Brain Stimulation Deep brain stimulation*

Initiate the electrophysiological monitoring. The final corroboration of the patient's target is the clinical assessment of sensory, motor, and speech areas. The neuropsychologist evaluating the patient must have a comprehensive understanding of complex sensory and speech processing functions. Certain tasks like complex linguistic expressions are encouraged to evaluate the speech apparatus. If the clinical examination excludes potential risk, the next step is permanent lesioning or deep brain stimulator placement. There are a variety of lesioning methods. Because of its reproducibility and precision, radiofrequency is the preferred choice in most medical centers. Once the target is selected, lesioning is subsequently performed using the Neuro50. The usual parameters we follow are 60 C for 60 seconds, three times.

The dopamine agonists used in the treatment of PD include apomorphine, bromocrip-tine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, and rotigotine. All of these agents activate D2 receptors, whereas pergolide has been shown to be a mild D1 agonist, and pramipexole may have higher affinity for D3 receptors (Table 1). Five subtypes of dopamine agonist receptors have been identified and may be classified into striatal (D1 and D2) receptors or cortical (D3, D4, and D5) receptors. The D3-5 receptors are present in the mesolimbic and mesocortical dopaminergic pathways. The D1-receptor (D1,5) family is associated with activation of adenylate cyclase and dopamine, and dopamine agonists activate the D2-receptor family (D2-4) (6). Postmortem examination of brains of patients with PD revealed upregulation of stri-atal D2 and downregulation of the D1 receptors. It is postulated that these changes lead to alteration of the indirect D2-mediated pathway and disinhibition of the...

The target lesion in one series included the dorsolateral STN and pallidufugal fibers (Forel's field H2). Postoperative chorea was mild and transient, except in one patient in whom the lesion was confined to the STN only. The chorea in this instance was controlled by the subsequent insertion of a deep brain stimulator in the field H2 fibers and zona incerta. A similar phenomenon was described by comparison of two cases by Chen et al. (108) that is, a subthalamotomy that included the dorsal extranuclear fibers of the zona incerta led to less dyskinesia than a lesion confined to the STN only. Tseng et al. (109) described another patient with a lesion large

Stereotactic surgeries for movement disorders were introduced in the late 1940s (1-3) but were not widely accepted due to significant morbidity, mortality, and limited knowledge of the appropriate target for symptomatic benefit. With advances in pharmacological therapy, particularly the availability of levodopa, these surgeries were rarely performed for Parkinson's disease (PD) until the late 1980s (4). Based on the limitations of drug treatments for PD, and a better understanding of the physiology and circuitry of the basal ganglia there has been a marked increase in the use of surgical treatments for PD. In addition, advances in surgical techniques, neu-roimaging, and improved electrophysiological recordings allow stereotactic procedures to be done more accurately leading to reduced morbidity. Deep brain stimulation (DBS) has largely replaced lesion surgery as the preferred procedure for PD. There are currently three targets for DBS in PD the ventral intermediate (VIM) nucleus of...

The major subcortical structures targeted for deep brain stimulation (DBS) or lesioning for the treatment of movement disorders include the nucleus ventralis intermedius (Vim) of the thalamus, the globus pallidus internal segment (GPi), and the subthalamic nucleus (STN). The major technical goal during surgery for movement disorders is to maximize both precision and safety. The methods for localization of the Vim, GPi, and STN are evolving and vary significantly between centers. Three types of methods may be used to determine target location before lesioning or chronic stimulator placement image-guided stereotactic localization, microelectrode mapping, and intraoperative test stimulation through the lesioning or DBS electrode, often called macrostimulation. The first of these is based on anatomy, whereas the latter two are based on physiology.

In additional studies involving neuropathic pain, Harke et al. found that SCS relieved pain in 23 of 28 patients with postherpetic neuralgia and 4 of 4 with acute herpes zoster (24). Katayama et al. found that deep brain stimulation led to pain control in 6 of 10 patients with phantom limb pain, whereas SCS was only efficacious in 6 of 19 patients (25).

Recently, deep brain stimulation (DBS) has revolutionized the field of movement disorders surgery. Deep brain stimulation, utilizing classic targets for movement disorders including the ventralis intermedius (VIM) nucleus of the thalamus for tremor 21,22 , globus pallidus for dystonia 23,24 , and the subthalamic nucleus of Luys for Parkinsonism 25 has shown significant promise in recent years. Subthalamic nucleus stimulation, in particular, results in long-term amelioration of all the cardinal signs of Parkinsonism. Deep brain stimulation has a number of advantages over ablative surgery, including the ability to adjust stimulation parameters to titrate effect and reversibility of the procedure.

Affective and behavioral changes (e.g., aggression, depression, mania) have also been reported as complications of deep brain stimulation (DBS), especially subthalamic nucleus (STN) DBS (81). Interestingly, depression has been infrequently reported to develop, as a result of thalamic and pallidal DBS (82). In a review of 23 articles reporting on the effect of STN DBS on mood state in PD, nine studies reported a mood elevating or antidepressant effect in 16.7 to 76 of patients, 13 studies reported a depressant effect in 2 to 33.3 of patients, and eight studies reported a mania-inducing effect in 4.2 to 8.1 of patients (83). In one series of 24 consecutive patients undergoing STN DBS, six patients (25 ) experienced significant worsening of mood and three were transiently suicidal despite motor improvement (84). In a series of 137 patients who underwent STN DBS, 16 (12 ) developed depression (85). Mood disturbances induced by STN DBS could be the result of stimulation spreading to...

Recent advances in functional imaging have allowed fMRI to be applied to a broad range of clinical disease processes. The combination of conventional BOLD Imaging with Diffusion Tensor Imaging and other physiologic techniques such as drug challenges holds great promise for understanding neuronal processes and the development of clinically meaningful diagnostic tests. Clinical applications of fMRI have largely relied on block style BOLD fMRI techniques to answer relatively simple questions regarding motor and language mapping in patients. These techniques have been applied most broadly in preoperative evaluations in the setting of brain tumours and epilepsy. More recent techniques such as event related paradigms and combinations of event and block style paradigms have allowed for better study of more sophisticated cognitive processes. These paradigms not only produce more complete assessments of cognitive processes presurgically, but they also open up the potential for non-invasive...

To answer questions about where in the brain as opposed to where in this brain, images from many subjects are often combined to form consensus mappings of the brain. These composite images help to standardize teaching of brain anatomy and support powerful statistical analyses for brain research. Composite brain images take on numerous forms the simplest is a group-average image, the backbone of cerebral blood-flow (CBF) studies using positron emission tomography (PET) 14,16,24,25 . Additionally, large-population composite brain images, formed from high-resolution three-dimensional (3D) magnetic resonance (MR) images, have been used to study anatomical variability in normal populations 10,36 . Whereas composite brain images are needed to represent population characteristics, individual brain images are required to diagnose and track brain problems in individual patients, i.e., they are the core of clinical decision making. A standard brain space is needed for consistent spatial...

We recommend confirming the location of the target with macrostimulation using the standard stimulator (Neuro50, F. L. Fischer Leibinger, Freiburg, Germany), given the fact that the mere introduction of the needle generates microsignals that can be somewhat confusing. The setup parameters of the stimulator are square waves of 2 to 100 Hz, 1 to 10 mV, 1 ms of duration. Once the accuracy of the target has been confirmed, we proceed with permanent lesioning. In the case of deep brain stimulation, the permanent electrode is left in place and secured, and the corresponding protocol is followed.

Parkinson's disease is one of the most common neurodegenerative diseases with a higher prevalence in older adults. It is a slowly progressive condition and has set the standard for research in neurodegeneration throughout the history of medicine. It was the first neurodegenerative disease for which the pathology was discovered, when I. Tretjakov first described the degenerated substantia nigra in 1919. The biochemistry was first described by A. Carlsson, and the transmitter deficit by O. Hornykiewicz. The accidental discovery of the selective neurotoxin (MPTP) for neurones of the substantia nigra in the 1980s has been of a similar importance, as it subsequently became possible to study Parkinson's disease in animal models. All these basic research achievements were the basis for groundbreaking progress in the field of therapy. Parkinson's disease was the first neurodegenerative disease for which transmitter replacement therapy was developed it was the first condition in medical...

Brain Blaster

Have you ever been envious of people who seem to have no end of clever ideas, who are able to think quickly in any situation, or who seem to have flawless memories? Could it be that they're just born smarter or quicker than the rest of us? Or are there some secrets that they might know that we don't?